Mohamed Siaj

Probing Charge Transfer at Surfaces Using Graphene Transistors

Graphene field effect transistors (FETs) are extremely sensitive to gas exposure. Charge transfer doping of graphene FETs by atmospheric gas is ubiquitous but not yet understood. We have used graphene FETs to probe minute changes in electrochemical potential during high-purity gas exposure experiments. Our study shows quantitatively that electrochemistry involving adsorbed water, graphene, and the substrate is responsible for doping. We not only identify the water/oxygen redox couple as the underlying mechanism but also capture the kinetics of this reaction. The graphene FET is highlighted here as an extremely sensitive potentiometer for probing electrochemical reactions at interfaces, arising from the unique density of states of graphene. This work establishes a fundamental basis on which new electrochemical nanoprobes and gas sensors can be developed with graphene.

Electrochemical impedance immunosensor based on gold nanoparticles-protein G for the detection of cancer marker epidermal growth factor receptor in human plasma and brain tissue.

A sensitive label-free impedimetric immunosensor for the detection of cancer biomarker epidermal growth factor receptor (EGFR) was developed with a limit of detection as low as 0.34 pg mL(-1) in PBS and 0.88 pg mL(-1) in human plasma. The gold nanoparticles were electrodeposited to modify the gold surface and to increase the electrochemical active area by a factor of approximately 3, i.e. by 68%. Protein G was used as scaffold for well oriented EGFR antibodies immobilization. Under optimal experimental parameters, the impedance changes were used for the detection of EGFR with a wide dynamic range of 1 pg mL(-1)-1 μg mL(-1). The immunosensor showed an excellent reproducibility and selectivity against biomarkers, murine double minute 2 and platelet derived growth factor receptor. The excellent analytical performance of the EGFR immunosensor in terms of selectivity, sensitivity and low detection limit might be attributed to the synergetic effect between the Au nanoparticles and the protein G scaffold. The matrix effect from mouse brain tissue homogenate was also studied and the immunosensor showed excellent recoveries ranging from 98.3% to 115% and RSD of 1.55-6.17. Finally, our developed strategy could open new avenues for clinical screening and prognosis of tumors.

110 GHz measurement of large-area graphene integrated in low-loss microwave structures

We report high-frequency scattering parameter measurement of large-area monolayer graphene integrated on low-loss quartz substrates. High-quality graphene was grown by chemical vapour deposition on copper, chemically hole doped, and transferred to quartz. Microwave measurements were performed from 0.01 to 110 GHz. Simple microwave models were used to extract graphene impedance parameters. We find that contact resistance is effectively shunted above 3 GHz. Atomically thin large area graphene behaves as a wideband resistor with negligible kinetic inductance and negligible skin effect.

Aptamer-based competitive electrochemical biosensor for brevetoxin‐2

Brevetoxins (BTXs) are very potent marine neurotoxins that increased in geographical distribution in the past decade causing the illness clinically described as neurological shellfish poisoning (NSP). The ethical problems as well as the technical difficulties associated with the currently employed analysis methods for marine toxins are encouraging the research for suitable alternatives to be applied in a regulatory monitoring regime. Here, we report an electrochemical biosensor platform for BTX-2 detection utilising aptamer as specific receptor. Using in vitro selection, high affinity DNA aptamers to BTX-2 were successfully selected for the first time from a large pool of random sequences. The binding of BTX-2 to aptamer pools/clones was monitored using fluorescence and electrochemical impedance spectroscopy (EIS). The aptamer BT10 exhibited the highest binding affinity to BTX-2, with a dissociation constant of 42nM. The effects of the incubation time, pH and metal ions concentrations on the aptamer-toxin binding were studied. The aptamer BT10 was used to construct a label-free competitive impedimetric biosensor for BTX-2 achieving a detection limit of 106pg/ml. We observed a high degree of cross reactivity of the selected aptamer to the two similar congeners, BTX-2 and -3, whereas no cross reactivity to other marine toxins was obtained. Moreover, the aptasensor was applied for the detection of BTX-2 in spiked shellfish extract showing a very high recovery percentage. We believe that the proposed aptasensor will facilitate the routine detection of BTX-2 in food samples.

Label-Free Voltammetric Aptasensor for the Sensitive Detection of Microcystin-LR Using Graphene-Modified Electrodes

The development of successful biosensing platforms is highly dependent upon the biorecognition properties of the recognition receptor and the sensitivity of the transducer of the binding signal. The integration of the high affinity and specificity of DNA aptamers with the unique properties of the carbon nanomaterial graphene offers an excellent avenue for sensitive and selective biosensing architectures. In this work, a highly sensitive and selective aptasensor which utilizes an unlabeled DNA aptamer assembled on a graphene electrode for microcystin-LR detection was developed. A facile strategy was used for the aptasensor fabrication on the basis of the noncovalent assembly of DNA aptamer on graphene-modified screen printed carbon electrodes. Assembly of the DNA aptamer on the graphene-modified electrodes caused a marked drop in the square wave voltammetric reduction signal of the [Fe(CN)6](4-/3-) redox couple. The presence of microcystin-LR, on the other hand, caused a dose-responsive increase in peak current, allowing the quantification of microcystin-LR through the measurement of peak current change. Under optimal conditions, the detection limit of the developed aptasensor was 1.9 pM in buffer, a concentration much lower than those offered by previously reported biosensors for microcystin-LR. The developed aptasensor also exhibited excellent selectivity for microcystin-LR with no detectable cross-reactivity to okadaic acid, microcystin-LA, and microcystin-YR. Moreover, the proposed aptasensor has been applied for the analysis of spiked tap water and fish samples showing good recovery percentages. This novel, simple, high-performance, and low-cost detection platform would facilitate the routine monitoring of microcystin-LR in real samples.

Selection and Identification of DNA Aptamers against Okadaic Acid for Biosensing Application

This work describes the selection and identification of DNA aptamers that bind with high affinity and specificity to okadaic acid (OA), a lipophilic marine biotoxin that accumulates in shellfish. The aptamers selected using systematic evolution of ligands by exponential enrichment (SELEX) exhibited dissociation constants in the nanomolar range. The aptamer with the highest affinity was then used for the fabrication of a label-free electrochemical biosensor for okadaic acid detection. The aptamer was first immobilized on the gold electrode by a self-assembly approach through Au-S interaction. The binding of okadaic acid to the aptamer immobilized on the electrode surface induces an alteration of the aptamer conformation causing a significant decrease in the electron-transfer resistance monitored by electrochemical impedance spectroscopy. The aptasensor showed a linear range for the concentrations of OA between 100 pg/mL and 60 ng/mL with a detection limit of 70 pg/mL. The dissociation constant of okadaic acid with the aptamer immobilized on the electrode surface showed good agreement with that determined using fluorescence assay in solution. Moreover, the aptasensor did not show cross-reactivity toward toxins with structures similar to okadaic acid such as dinophysis toxin-1 and 2 (DTX-1, DTX-2). Further biosensing applications of the selected aptamers are expected to offer promising alternatives to the traditional analytical and immunological methods for OA detection.

Faraday rotation in magnetically biased graphene at microwave frequencies

Faraday rotation is experimentally observed at microwave frequencies in a large-area graphene sheet biased with a static magnetic field, and interrogated by polarized fields in a hollow circular waveguide. A Faraday rotation of up to 1.5° and an isolation of more than 30 dB is observed, suggesting possible applications to graphene based isolators, circulators, and other non-reciprocal devices. An analytic model is developed for the scattering parameters of the measured structure. The model shows excellent agreement with the measurements and is used to extract the graphene conductivity, carrier density, and mobility.

Aptamer-Based Label-Free Impedimetric Biosensor for Detection of Progesterone

Rising progesterone (P4) levels in humans due to its overconsumption through hormonal therapy, food products, or drinking water can lead to many negative health effects. Thus, the simple and accurate assessment of P4 in both environmental and clinical samples is highly important to protect public health. In this work, we present the selection, identification, and characterization of ssDNA aptamers with high binding affinity to P4. The aptamers were selected in vitro from a single-stranded DNA library of 1.8 × 10(15) oligonucleotides showing dissociation constants (KD) in the low nanomolar range. The dissociation constant of the best aptamer, designated as P4G13, was estimated to be 17 nM by electrochemical impedance spectroscopy (EIS) as well as fluorometric assay. Moreover, the aptamer P4G13 did not show cross-reactivity to analogues similar to progesterone such as 17β-estradiol (E2) and norethisterone (NET). An impedimetric aptasensor for progesterone was then fabricated based on the conformational change of P4G13 aptamer, immobilized on the gold electrode by self-assembly, upon binding to P4, which results in an increase in electron transfer resistance. Aptamer-complementary DNA (cDNA) oligonucleotides were tested to maximize the signal gain of the aptasensor after binding with progesterone. Significant signal enhancement was observed when the aptamer hybridized with a short complementary sequence at specific site was used instead of pure aptamer. This signal gain is likely due to the more significant conformational change of the aptamer-cDNA than the pure aptamer upon binding with P4, as confirmed by circular dichroism (CD) spectroscopy. The developed aptasensor exhibited a linear range for concentrations of P4 from 10 to 60 ng/mL with a detection limit of 0.90 ng/mL. Moreover, the aptasensor was applied in spiked tap water samples and showed good recovery percentages. The new selected progesterone aptamers can be exploited in further biosensing applications for environmental, clinical, and medical diagnostic purposes.

Charge transfer hysteresis in graphene dual-dielectric memory cell structures

We report controlled charge transfer between large-area graphene and a dual-dielectric, silicon nitride/silicon oxide substrate. Graphene was grown on copper by chemical vapour deposition, transferred to the nitride substrates, and patterned into test structures. Hysteresis in conductance with varying gate voltage is easily understood in terms of electron transfer between graphene and nitride traps. Increased hysteresis with temperature suggests thermally activated charge transfer of a Poole-Frenkel or Schottky nature. A 7.3× change in graphene sheet resistance is observed at room temperature with the nitride in a charged and discharged state.

DNA aptamers selection and characterization for development of label-free impedimetric aptasensor for neurotoxin anatoxin-a

High affinity DNA aptamers against anatoxin-a (ATX), the smallest potent neurotoxin (Mol. Wt, 165.23 Da) were selected and identified in vitro using the systematic evolution of ligands by exponential enrichment (SELEX) approach. Aptamers with dissociation constants (Kd) of nanomolar range were isolated. The aptamer sequence of highest affinity was used to design a label-free impedance based aptasensor to assay ATX, for which there are no reported biosensors so far. The aptamer self assembled monolayer is formed on a gold electrode using the disulfide modified aptamer. The assembly process of the aptasensor was characterized using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Upon ATX binding to the immobilized aptamer, a significant decrease in the electron-transfer resistance was observed as a result of the aptamer conformation change, which is used as the sensor signal. The aptasensor showed a limit of detection of 0.5 nM and a wide linear range for ATX concentrations between 1 nM and 100 nM. The Kd of anti-ATX aptamer was calculated by electrochemical methods as well as the fluorescence. Interestingly, the Kd that was calculated from the aptasensor signal showed a lower value implying that the anchoring of the aptamer on the Au surface enhanced its affinity to ATX. The ATX aptasensor showed high stability as well as high specificity against common cynaobacterial toxins. Further development of biosensors that use anatoxin-a binding aptamers as a new recognition receptors could provide potential alternatives to the traditional assays for fast and simple monitoring of anatoxin-a.